The present invention relates to an atmospheric pressure ionization mass spectrometer in which mass spectrometry is performed by ionizing a sample in an atmospheric pressure environment.
In order to analyze a trace of an organic chemical compound with a high accuracy in various kinds of organic chemical compounds existing in an environment, a food or a body, a liquid chromatograph-mass spectrometer (an LC/MS apparatus) is growing to be widely used. The apparatus is formed by combining a liquid chromatograph (an LC) of separation means and a mass spectrometer (an MS) of a high sensitive qualitative and quantitative analysis means, and is growing to be used in various fields of the pharmacology, the medical science, the chemistry, the environmental chemistry and so on.
An important thing is the LC/MS apparatus is that the MS of a detector of the LC as the separation means is preferably capable of accepting all the analysis conditions constructed solely by the LC. However, there is a large problem in that the above premise is actually not satisfied in measuring of the LC/MS apparatus.
In an LC, in order to obtain better reproducibility by ameliorating separation and quantitativeness, a buffer solution containing various kinds of nonvolatile inorganic salts and inorganic acids is used as a mobile phase. Phosphate buffer solution is a typical one. Phosphate buffer solution is widely used in the LC because it has no absorption band in the ultraviolet range and can be used in a wide range of PH.
On the other hand, the mobile phase containing the nonvolatile salt (phosphate buffer solution or the like) can not be used in the LC/MS apparatus. This is because the LC/MS apparatus is an apparatus in which analysis is performed using a high vacuum mass spectrometer through the processes of nebulization, ionization and evaporation. That is, after being nebulized, the nonvolatile salt precipitates in an ion sampling aperture and an ion sampling capillary tube to clog them. Particularly, the ion sampling aperture and the ion sampling capillary tube are heated up to nearly 200xc2x0 C. in order to prevent the evaporated water from condensing. Therefore, the nonvolatile salt is accelerated to be precipitated in the ion sampling aperture and the ion sampling capillary tube. In addition, phosphoric acid produces poly-phosphoric acid by being heated. The poly-phosphoric acid rapidly grows in crystals in the aperture and the capillary tube to clog the aperture and the capillary tube. Since a flow rate of a gas containing sample ions introduced in the MS through the aperture and the capillary tube is varies with time due to the salt precipitated with time even if the aperture and the capillary tube are not clogged yet. Therefore, stable measurement can not be expected with the LC/MS apparatus.
Since nonvolatile salts, bases and acids can not be used in the LC/MS apparatus from the above reason, analysis is performed using a buffer solution containing a volatile acid (acetic acid or the like), a volatile base (ammonia or the like) and a volatile salt (ammonium acetate or the like) instead of the nonvolatile buffer solution. Therefore, the analytical conditions constructed and established for the LC based on a phosphate buffer solution is abandoned, and accordingly an analyst is required to take the trouble of newly constructing the other analytical conditions for the LC/MS apparatus.
Some means to solve the trouble are proposed.
Japanese Patent Application Laid-Open No.61-175560 discloses a technology that a sample solution after being separated by the LC and just before being introduced into the LC/MS interface is mixed with a solution containing a chelating agent to precipitate and remove nonvolatile components so that only volatile components are transported into the MS together with the sample component. This method has a problem in that the separability is largely deteriorated because the sample component carefully separated by the column diffuses in a large volume of space for reaction and precipitation. In addition to this, the sample component is adsorbed to the precipitate to be removed together with the precipitate, and consequently practical high sensitive measurement can not be attained.
Japanese Patent Application Laid-Open No.6-52826 discloses a technology that sample component is extracted online into an organic solution by mixing the organic solution with a mobile phase, and the organic solution is let pass through an organic polymer film to separate nonvolatile salts from the solution, and then transported into the MS. An advantage of this method is that the sample component can be extracted online. On the other hand, it is inevitable that the separation performance and the sensitivity are decreased by increase in the dead volume after separation in the column. Further, it is impossible to measure a high polar compound which is difficult to be transferred to an organic solution.
Japanese Patent Application Laid-Open No.6-201650 and Japanese Patent Application Laid-Open No.6-186203 disclose another method in which nonvolatile salts are removed and sample components are selectively introduced into the LC/MS interface. In this method, an eluted sample component is once trapped to a trap column, and then the trap column is washed with water by switching a valve of the LC/MS apparatus to remove nonvolatile salts. After that, by switching the valve again, the sample component is eluted from the trap column using an organic solution to be transferred into the MS. According to this method, nonvolatile salts can be removed with a very high efficiency. Further, the method has an advantage in capability of high sensitive measurement and so on since the sample component is once trapped and then eluted. On the other hand, the method has a large disadvantage in that the apparatus becomes complex and expensive, and online removing of all salts over the whole chromatograph (over the whole range of the samples) though specified components can be removed.
Japanese Patent Application Laid-Open No.5-325882 proposes a technique different from the above-mentioned technique in order to solve this problem.
A component from an LC is nebulized and ionized in an LC/MS interface. The nebulized flow including ions travels straight. At a position midway of the trajectory, the ions are deflected from the nebulized flow by a deflector applied with a voltage. The ions are collected into a differential pumping system through an ion sampling aperture, and guided to a high vacuum mass analysis portion to be mass-analyzed. Nonvolatile salts in the nebulized flow travel straight without being affected by the electric field of the deflector in the forms of fine liquid droplets, fine particles or clusters formed of fine liquid droplets and fine particles, and collided against a collecting plate to be trapped. This technique is a good method capable of online removing the nonvolatile components. However, when a phosphate buffer solution of 10 mM is actually let flow at a flow rate of 1 ml/min, approximately 1 g of the phosphates is accumulated on the collecting plate by measurement in one day (8 hours). The precipitated phosphates are formed in flossy crystals of which the apparent specific gravity is extremely small. Therefore, the collecting plate is fully filled with the phosphate crystals in a short time. Further, since the crystals are extremely brittle and soft. Therefore, the crystals are sometimes crushed by the high speed nebulizing gas flow and sucked into the ion sampling aperture to clog the aperture. Japanese Patent Application Laid-Open No.5-325882 discloses an idea that the trapped substances are removed by heating the collecting plate, but phosphoric acid and inorganic acids and bases can not be removed by heating. This method is effective in using a mobile phase containing nonvolatile salts for a short time, but ineffective in stably measuring for a longtime.
Japanese Patent Application Laid-Open No.61-95244 discloses an LC/MS apparatus in which a buffer solution containing nonvolatile salts is used as an eluent for the liquid chromatograph. When nonvolatile salts are contained in an eluent, the salts are precipitated and attached to the heated nebulization capillary tube to cause clogging of the heated capillary tube. This is likely to occur at the time of ending of measurement, that is, particularly at the time when the solution is stopped to flow. In order to solve this problem, in the LC/MS apparatus disclosed in Japanese Patent Application Laid-Open No.61-95244, a solution capable of dissolving the salts is let flow through the heated capillary tube at the time of ending of measurement replacing the eluent to wash the inside of the heated capillary tube and wash away the precipitated salts with the solution. The nonvolatile salts also clog a sampling aperture electrode in the mass analysis portion. Therefore, Japanese Patent Application Laid-Open No.61-95244 also proposes that the solution capable of dissolving the salts is nebulized and let flow toward the sampling aperture to wash away the precipitated salts at the time of not performing measurement. However, since the technology disclosed in Japanese Patent Application Laid-Open No.61-95244 can not wash away the nonvolatile salts during measurement, the method has a problem in that stable measurement can not be continued for a long time. In addition to this, when the washing solution is sprayed toward the sampling aperture, the washing solution enters into the mass analysis portion to make it difficult to maintain a vacuum condition of the inside.
An object of the present invention is to provide an atmospheric pressure ionization mass spectrometer which can prevent effects of nonvolatile salts on the mass analysis without deteriorating the vacuum condition of the mass analysis portion by the preventing action.
Another object of the present invention is to provide an atmospheric pressure ionization mass spectrometer which can perform stable measurement practically without effects of nonvolatile salts on the mass analysis.
From one aspect, the present invention is characterized by an atmospheric pressure ionization mass spectrometer comprising an ion generating means for generating ions by nebulizing a sample solution in an atmospheric pressure environment; a particle collector disposed on a main axis of a nebulized flow of the sample solution; a mass spectrometer for mass analyzing ions passing along an axis departing from the main axis, the ions being generated by the ion generating means; and a washing means for washing the particle collector.
From another aspect, the present invention is characterized by an atmospheric pressure ionization mass spectrometer comprising an ion generating means for generating ions by nebulizing a sample solution in an atmospheric pressure environment; an evacuation duct disposed on a main axis of a nebulized flow of the sample solution; and a means for evacuating the nebulized flow passing along the main axis through the evacuation duct.